Sonic hedgehog opposes epithelial cell cycle arrest.

Sonic hedgehog opposes epithelial cell cycle arrest.
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DOI:
10.1083/jcb.147.1.71
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发表时间:
1999-10-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Khavari PA
Khavari PA
中科院分区:
其他
文献类型:
--
作者:
Fan H;Khavari PA

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复层上皮显示增殖和细胞周期停滞之间的平衡,这种平衡在基底细胞癌(BCC)中被破坏。Sonic hedgehog(Shh)通路的激活似乎足以诱导BCC,然而,它这样做的方式是未知的。Shh诱导的表皮增生伴随着体内正常生长停滞的基底上细胞的持续细胞增殖。表达Shh的细胞不能退出S期和G2/M期响应钙诱导的分化,也抵抗复制生长能力的耗尽。此外,Shh阻断p21 CIP 1/WAF 1诱导的生长停滞。这些数据表明,Shh促进肿瘤形成的上皮细胞周期阻滞的正常刺激。
Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity. In addition, Shh blocks p21CIP1/WAF1-induced growth arrest. These data indicate that Shh promotes neoplasia by opposing normal stimuli for epithelial cell cycle arrest.
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